Endosomal trafficking of the ligated FcvarepsilonRI receptor.
In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcvarepsilonRI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15min after ligation. Minimal co-localization of FcvarepsilonRI with Rab5 was observed by 30min, followed by its appearance in the Rab7(+) late endosomes and lysosomes at later time points. During endosomal sorting, FcvarepsilonRIalpha and gamma subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated FcvarepsilonRI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of FcvarepsilonRI in endosomes.
Fattakhova
Gul'nar V
GV
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, United States.
Masilamani
Madhan
M
Narayanan
Sriram
S
Borrego
Francisco
F
Gilfillan
Alasdair M
AM
Metcalfe
Dean D
DD
Coligan
John E
JE
D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000235:genetics / Q000276:immunology*; D007152:Immunologic Capping / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008247:Lysosomes / Q000235:genetics / Q000276:immunology*; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D051381:Rats; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000276:immunology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins
D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D000090802:rab7 GTP-Binding Proteins; C000716466:rab7 GTP-binding proteins, rat; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D020691:rab GTP-Binding Proteins